Positive changes in behavior are essential to improved health. Whereas such changes can often be instituted through intervention, long-term maintenance of these changes can be very difficult, as highlighted in this RFA. An understanding of how behaviors can be replaced and maintained is necessary in order to most effectively promote sustained beneficial changes in health-related behavior. The work proposed here will focus on understanding the brain systems that support the implementation and maintenance of behavioral change. Our work is based on the idea that there are fundamental differences between first-learned behaviors and later- learned behaviors, which result in lasting difficulties in maintenance of new behaviors in comparison to the old ones that they are meant to supplant. Although later-learned behaviors are often viewed as "replacing" first- learned ones, there is substantial behavioral evidence that first-learned behaviors are not over-written as they are extinguished, but instead are retained in a latent state. Further, it appears that maintenance of a secondary behavior requires continued suppression of the primary one in addition to acquisition of the new response. Finally, secondary behaviors appear to be substantially more context-dependent than primary ones, which results in decreased generalization to new situations. Using a combination of sophisticated neuroimaging techniques, the proposed work will characterize the brain processes that are associated with first-learned versus later-learned behaviors, and test a set of methods to improve the resilience of later-learned behaviors, with the ultimate goal of improving the long-term effectiveness of behavior change interventions. PUBLIC HEALTH RELEVANCE: Many public health problems, from obesity to heart disease to cancer to drug abuse, could be reduced by changes in behavior, but it is notoriously hard to overcome unhealthy behaviors in a lasting way. The research proposed here would investigate a previously neglected reason for this difficulty, and provide an understanding of the basic brain mechanisms that may make it difficult to overcome bad habits as well as testing several possible ways to improve the long-term effectiveness of behavioral change.